The reflex is a basic unit of behavior and a building block of many forms of learning and memory. Associative changes in the reflex have recently been described but they lack behavioral laws and the neural substrates are unknown. This gap in knowledge is an important problem because associative changes in the reflex may have significant implications for many forms of learning. Without understanding this new form of reflex modification, a complete understanding of the behavioral complexity and biological basis of many forms of learning is unlikely. Our long-range goal is to understand how learning modifies behavior in order to develop preventive and therapeutic strategies for learning and memory disorders. The objective of this application is to characterize the behavioral laws and identify the potential neural substrates of the conditioning-specific reflex modification that occurs after classical conditioning of the rabbit's nictitating membrane response (NMR). The central hypothesis of the application is that classical conditioning induces changes in the unconditioned response - detectable in the absence of the conditioned stimulus - that can be described, quantified, and localized. This hypothesis is based on strong evidence from behavioral experiments showing significant changes in the reflex following classical conditioning. The rationale for the proposed research is that once behavioral laws governing learning-specific changes in the reflex are known, they may provide a model for new and innovative approaches to the treatment of learning and memory disorders such as post traumatic stress disorder. The objective of this application will be accomplished by pursuing two specific aims: 1) Characterize the behavioral laws governing conditioning-specific reflex modification and 2) Identify potential neural substrates of conditioning-specific reflex modification. The proposed work is innovative because it combines a novel behavioral finding - conditioning-specific reflex modification - with a very well understood learning paradigm - classical conditioning of the rabbit NMR. The research is significant because it will provide strategies for preventive and therapeutic interventions for the growing numbers of persons in this country with disorders in learning and memory, such as post-traumatic stress disorder, as well as provide an understanding of the biological processes that underlie learning and memory.